Efficacy of Melatonin in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis
8 affiliations
- 1Department of Medicine, Cooper University Health Care, Camden, NJ, USA
- 2Karachi Medical and Dental College, North Nazimabad, Karachi, Sindh, Pakistan
- 3Department of Medicine, Dow University of Health Sciences, Karachi, Sindh, Pakistan
- 4Department of Medicine, University of Maryland Midtown, Baltimore, MD, USA
- 5Department of Medicine, Touro University, New York, NY, USA
- 6New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA
- 7The University of Kansas School of Medicine, Kansas City, KS, USA
- 8Cooper Medical School of Rowan University, Camden, NJ, USA
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the leading cause of chronic liver disease globally. Oxidative stress, inflammation, and hepatocellular necrosis play central roles in its pathogenesis. Emerging evidence highlights melatonin as a promising therapeutic agent for MASLD. This systematic review and meta-analysis aimed to evaluate the efficacy of melatonin in MASLD management.
Methods: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science from inception through December 2025 for randomized and non-randomized controlled clinical trials comparing melatonin supplementation with placebo, no treatment, or an active comparator in adults with MASLD. Dichotomous outcomes were pooled as risk ratios (RRs) using the Mantel–Haenszel method and continuous outcomes as mean differences (MDs) using the inverse-variance method, both under random-effects models. In every trial the control arm received the same background management as the melatonin arm (placebo, essential phospholipids, statin therapy, or lifestyle advice) without melatonin; no trial compared melatonin with an active pharmacological comparator.
Results: Eleven controlled trials (nine randomized, two non-randomized; 548 participants: 300 melatonin, 248 control) were included. In the primary analyses, melatonin was associated with reductions in total cholesterol (MD: −16.80 mg/dL, 95% confidence interval (CI): −29.13 to −4.47, P = 0.008; I2 = 76%) and low-density lipoprotein (LDL) cholesterol (MD: −52.4 mg/dL, 95% CI: −100.52 to −4.27, P = 0.03; I2 = 96%), in interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and in body weight and waist circumference, and with a lower proportion of participants with grade III steatosis at follow-up (RR: 0.23, 95% CI: 0.07–0.77; two trials). No significant differences were found for grade I or II steatosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), triglycerides, high-density lipoprotein (HDL), fasting blood sugar, systolic/diastolic blood pressure, or high-sensitivity C-reactive protein (hs-CRP). Reductions in ALT, AST, GGT, and triglycerides were observed only in exploratory sensitivity analyses after exclusion of individual trials. Heterogeneity was high (I2 > 75%) for several outcomes, and nine of the 11 trials were placebo-controlled.
Conclusion: Melatonin supplementation was associated with modest improvements in total and LDL cholesterol, selected inflammatory markers, and anthropometric measures, but not in liver enzymes or grade I–II steatosis. Given the small number of trials, the inclusion of non-randomized designs, high heterogeneity, heterogeneous comparators, and the exploratory nature of the sensitivity analyses, these findings are preliminary. Melatonin may merit evaluation as an adjunctive therapy in MASLD, but larger, well-designed randomized trials with standardized comparators and systematic safety reporting are required.
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BibTeX
@article{singh2026efficacy,
title = {{Efficacy of Melatonin in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis}},
author = {Avneet Singh and Fariha Hasan and Marium Zahid and Syeda Hafsa Qadri and Mohammed Aloqaily and Zehara Abidi and Alexa Conner and Alexander Garcia and Dushyant Singh Dahiya and Krysta Contino and Christina Tofani and Anthony Infantolino and Satyajeet Roy},
journal = {Journal of Clinical Medicine Research},
year = {2026},
month = oct,
doi = {10.14740/jocmr6688},
url = {https://europepmc.org/article/PMC/PMC13719654},
note = {CC BY},
}
RIS
TY - JOUR
TI - Efficacy of Melatonin in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis
AU - Avneet Singh
AU - Fariha Hasan
AU - Marium Zahid
AU - Syeda Hafsa Qadri
AU - Mohammed Aloqaily
AU - Zehara Abidi
AU - Alexa Conner
AU - Alexander Garcia
AU - Dushyant Singh Dahiya
AU - Krysta Contino
AU - Christina Tofani
AU - Anthony Infantolino
AU - Satyajeet Roy
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine Research
DO - 10.14740/jocmr6688
UR - https://europepmc.org/article/PMC/PMC13719654
AB - Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the leading cause of chronic liver disease globally. Oxidative stress, inflammation, and hepatocellular necrosis play central roles in its pathogenesis. Emerging evidence highlights melatonin as a promising therapeutic agent for MASLD. This systematic review and meta-analysis aimed to evaluate the efficacy of melatonin in MASLD management. Methods: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science from inception through December 2025 for randomized and non-randomized controlled clinical trials comparing melatonin supplementation with placebo, no treatment, or an active comparator in adults with MASLD. Dichotomous outcomes were pooled as risk ratios (RRs) using the Mantel–Haenszel method and continuous outcomes as mean differences (MDs) using the inverse-variance method, both under random-effects models. In every trial the control arm received the same background management as the melatonin arm (placebo, essential phospholipids, statin therapy, or lifestyle advice) without melatonin; no trial compared melatonin with an active pharmacological comparator. Results: Eleven controlled trials (nine randomized, two non-randomized; 548 participants: 300 melatonin, 248 control) were included. In the primary analyses, melatonin was associated with reductions in total cholesterol (MD: −16.80 mg/dL, 95% confidence interval (CI): −29.13 to −4.47, P = 0.008; I2 = 76%) and low-density lipoprotein (LDL) cholesterol (MD: −52.4 mg/dL, 95% CI: −100.52 to −4.27, P = 0.03; I2 = 96%), in interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and in body weight and waist circumference, and with a lower proportion of participants with grade III steatosis at follow-up (RR: 0.23, 95% CI: 0.07–0.77; two trials). No significant differences were found for grade I or II steatosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), triglycerides, high-density lipoprotein (HDL), fasting blood sugar, systolic/diastolic blood pressure, or high-sensitivity C-reactive protein (hs-CRP). Reductions in ALT, AST, GGT, and triglycerides were observed only in exploratory sensitivity analyses after exclusion of individual trials. Heterogeneity was high (I2 > 75%) for several outcomes, and nine of the 11 trials were placebo-controlled. Conclusion: Melatonin supplementation was associated with modest improvements in total and LDL cholesterol, selected inflammatory markers, and anthropometric measures, but not in liver enzymes or grade I–II steatosis. Given the small number of trials, the inclusion of non-randomized designs, high heterogeneity, heterogeneous comparators, and the exploratory nature of the sensitivity analyses, these findings are preliminary. Melatonin may merit evaluation as an adjunctive therapy in MASLD, but larger, well-designed randomized trials with standardized comparators and systematic safety reporting are required.
SN - 1918-3003
SN - 1918-3011
ER -